Of the numerous biological agents that may be used as weapons, the Working Group on Civilian Biodefense, comprised of 21 representatives from academic medical, research, government, military and public health institutions, has identified a limited number of organisms that could cause disease and deaths in sufficient numbers to cripple a city or region. Anthrax is one of the most serious of these diseases.

For centuries, anthrax has caused disease in animals and, uncommonly, serious illness in humans throughout the world. Research on anthrax as a biological weapon began more than 80 years ago. Today, while at least 17 nations are believed to have offensive biological weapons programs, it is uncertain how many are working with anthrax. Iraq has acknowledged producing and weaponizing anthrax.

The accidental aerosolized release of anthrax spores from a military microbiology facility in Sverdlovsk in the former Soviet Union in 1979 resulted in at least 79 cases of anthrax infection and 68 deaths and demonstrated the lethal potential of anthrax aerosols. Much of what we know about anthrax deaths in humans is from the Sverdlovsk experience.

Epidemiology

Naturally occurring anthrax is a disease acquired following contact with anthrax-infected animals or anthrax-contaminated animal products.

In humans, three types of anthrax infections occur: inhalational, cutaneous (skin), and gastrointestinal.

Cutaneous anthrax is the most common naturally occurring form. Disease typically follows exposure to anthrax-infected animals. Gastrointestinal anthrax is rare but often fatal, and follows consumption of insufficiently cooked contaminated meat. A case of gastrointestinal anthrax has never been documented in the United States. Naturally occurring inhalation anthrax is now a rare cause of human disease. Historically, wool sorters at industrial mills were at highest risk, and the disease was known as woolsorters' disease. Only 18 cases of inhalational anthrax were reported in the United States from 1900 to 1978, with the majority occurring in special-risk groups including goat hair mill or goatskin workers and wool or tannery workers. No case of inhalation anthrax has been reported in the United States from 1978 until the recent case in Florida, making even a single case a cause for alarm today.

As was demonstrated at Sverdlovsk in 1979, inhalational anthrax is expected to account for the vast majority of deaths following the use of anthrax as an aerosolized biological weapon. In the Sverdlovsk experience, there were no deaths in patients developing cutaneous anthrax. There is little information available about the risks of direct contamination of food or water with anthrax spores. Although human infections have been reported, experimental efforts to infect monkeys by direct gastrointestinal instillation of anthrax spores have not been successful.

Microbiology

Anthrax is caused by a bacteria called Bacillus anthracis. It is what is referred to as a "spore-forming" bacteria. Spores are to bacteria what seeds are to apples. Spores can persist for decades in a variety of harsh environments such as soil, and when conditions permit (such as inside cattle or a human), may develop into the full bacteria. A spore acts like a bacteria in suspended animation, waiting to become the bacteria again. Bacillus anthracis derives its name from the Greek word for coal, anthrakis, because the cutaneous disease causes black, coal-like skin lesions.

Clinical manifestations

Inhalation anthrax

Inhalation anthrax follows inhalation of spore-bearing particles. Surviving spores are taken up by white cells in the lungs and transported to the lymph nodes in the spaces around the heart, where "germination" of the spores may occur up to 60 days later. The reasons for variation in germination time are not known. In Sverdlovsk, cases occurred from 2 to 43 days after exposure.

Once germination occurs, disease follows rapidly. The growing volume of bacteria release toxins that lead to bleeding, swelling and tissue destruction around the heart and between the lungs (the area of the chest known as the mediastinum). Once a certain amount of toxin has been produced, even killing all the bacteria by antibiotics will not prevent death.

Early diagnosis of inhalation anthrax would be difficult and would require a high index of suspicion. Experience from Sverdlovsk suggests that the disease may come in two stages. Patients first develop a spectrum of non-specific symptoms, including fever, shortness of breath, cough, headache, vomiting, chills, weakness, abdominal pain and chest pain. At this point, blood tests are not specific for any particular disease. This stage can last from hours to a few days. In some, a transient period of improvement may follow. Other patients progress directly to the second "fulminant" stage.

The second, more severe stage develops abruptly, with sudden fever, shortness of breath, sweating and shock. The mediastinum can enlarge dramatically, compressing the heart and lungs. Up to half of the patients develop bleeding in their central nervous system and brain (anthrax meningitis), leading to headache, delirium and coma. In this second stage of illness, shock progresses rapidly; death sometimes occurs within hours. The records of Sverdlovsk are difficult to interpret, but it appears that in fatal cases, the interval between onset of symptoms and death averaged 3 days. The mortality rate for inhalation anthrax approaches 100%, and therapy is usually unsuccessful. Anthrax meningitis is usually fatal.

Cutaneous anthrax

Cutaneous anthrax follows the deposition of the bacteria or spores into the skin through cuts or abrasions or insects. Areas of exposed skin such as arms, hands, face and neck are the most frequently affected. After the spore germinates in the skin tissue, toxin production results in local swelling initially. Then small blisters appear and lead to the development of black scabs that dry and fall off in one to two weeks. Lymph nodes near the skin lesions can swell and get painful. Antibiotics do not change the course of the skin lesions, but they can prevent the disease from getting beyond the skin. Without antibiotics, the mortality rate has been reported to be as high as 20%; with antibiotics, death due to cutaneous anthrax is rare. Those that die eventually show signs similar to the fulminant form of inhalational disease.

Gastrointestinal anthrax

Gastrointestinal anthrax occurs following deposition and subsequent germination of spores in the upper or lower gastrointestinal tract. The former results in swelling and infection in the mouth or esophagus. The latter results in intestinal manifestation such as nausea, vomiting, bloody diarrhea and abdominal pain. If the disease becomes advanced, it can eventually resemble the end stages of the inhalation type. The mortality from treated intestinal anthrax is approximately 50%.

Michael E. Pezim, MD
in association with the MediResource Clinical Team